Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[n.2.1] Skeletons. Issue 28 (6th June 2019)

• Record Type: Journal Article
• Authors: Tan, Tong‐De; Zhu, Xin‐Qi; Bu, Hao‐Zhen; Deng, Guocheng; Chen, Yang‐Bo; Liu, Rai‐Shung; Ye, Long‐Wu
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 28(2019)
• Page Start: 9632
• Page End: 9639
• Publication Date: 2019-06-06
• Subjects: copper -- cyclizations -- heterocycles -- stereoselectivity -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201904698
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Catalytic cycloisomerization‐initiated cascade cyclizations of terminal alkynes have received tremendous interest, and been widely used in the facile synthesis of a diverse array of valuable complex heterocycles. However, these tandem reactions have been mostly limited to noble‐metal catalysis, and are initiated by an exo ‐cyclization pathway. Reported herein is an unprecedented copper‐catalyzed endo ‐cyclization‐initiated tandem reaction of indolyl homopropargyl amides, where copper catalyzes both the hydroamination and Friedel–Crafts alkylation process. This method allows the practical and atom‐economical synthesis of valuable bridged aza‐[ n .2.1] skeletons ( n =3–6) with wide substrate scope, and excellent diastereoselectivity and enantioselectivity by a chirality‐transfer strategy. Moreover, the mechanistic rationale for this novel cascade cyclization is also strongly supported by control experiments, and is distinctively different from the related gold catalysis. Abstract : A copper‐catalyzed endo ‐cyclization‐initiated tandem reaction of indolyl homopropargyl amides is achieved, where copper catalyzes both the hydroamination and Friedel–Crafts alkylation process. The anti‐Markovnikov addition outcompetes the typical Markovnikov addition, and this method allows the practical and atom‐economical synthesis of valuable bridged aza‐[ n .2.1] skeletons ( n= 3–6) with wide substrate scope and excellent diastereo‐ and enantioselectivity.